Mutation in the hemagglutinin of A/N-WS/33 influenza virus recombinants influencing sensitivity to trypsin and antigenic reactivity

Abstract

The hemagglutination activity of the influenza virus A/RI/5-/57 (H2N2) is resistant to trypsin treatment, but that of A/N-WS/33 (HONI) is rapidly lost on exposure to trypsin. Two recombinant viruses, both of which derive their HO hemagglutinin from NWS and their N2 neuraminidase from RI/5 −, show different sensitivity to trypsin. The hemagglutination activity of X-12, like that of NWS, is rapidly lost, whereas the activity of X-29 shows a trypsin sensitivity intermediate between that of the NWS and RI/5 − parental viruses. Trypsin sensitivity of hemagglutination activity is a phenotypic marker that is associated in the present case with minimal antigenic differences as revealed by conventional serological techniques using subtype-specific antisera. The specific property of slow trypsin sensitivity, which can revert to fast trypsin sensitivity, is probably due to one or a limited number of point mutations in the hemagglutinin gene. The selection of minor antigenic variants may occur fortuitously during exposure of the virus to nonimmunologic pressures. Although X-12 and X-29 viruses differ with respect to ratios of hemagglutinin and neuraminidase proteins per virion, neither the amount nor the antigenic nature of the neuraminidase protein influences the relative trypsin sensitivity of the associated viral hemagglutinin. Selective removal of hemagglutinin spikes by trypsin has revealed the morphology and spacing of the neuraminidase spikes in situ.